The goal of this Exploratory Clinical Sequencing project is to integrate CLIA-certified germ line and tumor exome sequencing information generated by the Whole Genome Laboratory into the care of childhood cancer patients with high-risk solid tumors and brain tumors at the Texas Children's Cancer Center. Given the clinical nature of the project the dual principal investigators will be Drs. Donald W. Parsons and Sharon E. Plon, board-certified pediatric oncologist and medical geneticist, respectively. We will assess the impact of whole exome sequence data reported by a novel web-based platform with links to existing data for each variant reported and presented through a graphical display that will facilitate physician disclosure of complex data to parents. We will evaluate physician-parent communication and clinical decision-making in the context of two clinical questions (1) How does the availability of tumor whole exome sequence data affect physician recommendations regarding enrollment on specific clinical trials and the treatment plans chosen in the scenario of tumor recurrence? (2) How does the availability of germline whole exome sequence data affect cancer surveillance for patients and genetic testing and cancer surveillance for family members? Quantitative analysis of physician communication in disclosure of genome-scale data will be performed. Parental understanding and preferences for receiving genome scale data will be assessed. Ethical issues related to the appropriate use and reporting of whole exome data including possible incidental findings in a pediatric setting will be addressed. Baylor College of Medicine is ideally suited to conduct this study with the longstanding clinical oncology and cancer genetics practices, extensive expertise in genomics through the Human Genome Sequencing Center, the largest academic CLIA-certified molecular diagnostic laboratory in the United States and a track record of scholarship in ethical and social implications of genomics in the Center for Medical Ethics and Health Policy and physician-patient/parent communication in the Division of Health Outcome Services. PUBLIC HEALTH RELEVANCE: The recent deluge of genetic data has translated into an exponential increase in the number of molecularly targeted pediatric cancer clinical trials. Therefore, an investigation of the impact of genomic sequence data on decision making of physicians and parents in relation to cancer risk and selection of treatment at the time of tumor recurrence would have significant impact and relevance for the field of pediatric oncology.